The elucidation of the mode of biosynthesis of sterols and related polycyclic isoprenoids has led to development by man of highly efficient non-enzymic synthesis of sterols from linear acyclic polyenes. While transannular cyclizations are known to play an important role in the biosynthesis of certain sesquiterpenoids, such transannular cyclizations have not been explored as a potential means of synthesis of tri- and tetra-cyclic structures. The aim of this research is to examine biogenetic-like olefin cyclization within macrocyclic polyenes--the result of which is a totally new approach to sterol synthesis. General synthetic approaches will be developed for the highly functionalized macrocyclic precursors required. The chemical reactivity and cyclizations of these macrocycles will be analyzed in light of their preferred conformations as deduced by spectroscopic measurements and computer-assisted conformational analysis. This information should help define the conformational requirements for biogenetic-like olefin cyclization. The compounds prepared in this research are analogs of some naturally occurring macrocyclic diterpenes and macrolide antibiotics, none of which have been synthesized. This study should be useful in understanding the chemistry and conformational properties of these biologically important natural products.